{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:52:36Z","timestamp":1773010356642,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,2,25]]},"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    is a major human pathogen responsible for severe infections that necessitate alternative therapeutic strategies. Its key virulence factor \u03b1\u2010hemolysin (Hla) mediates host cell damage via pore formation, making it an attractive target for antivirulence interventions. Here, we report the development of a high\u2010throughput cellular assay measuring toxin\u2010induced calcium influx. Its application led to the identification of thiadiazole\u2010based small molecule inhibitors of Hla. Structure\u2013activity relationship studies with 18 analogs led to inhibitors with a cellular potency up to 5.4 \u00b5M. X\u2010ray crystallography of Hla in complex with compound\n                    <jats:bold>1<\/jats:bold>\n                    revealed that the thiadiazole bound a hydrophobic pocket at the interface of the amino latch and prestem domains, exerting a dual mechanism that blocks stem loop unfolding as well as membrane attachment. These findings introduce thiadiazoles as a novel chemical class of antivirulence therapeutics against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    infections.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202501098","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:08:56Z","timestamp":1772968136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Imidazo[2,1\u2010b][1,3,4]thiadiazole Derivative Inhibits the Virulence Factor \u03b1\u2010Hemolysin by Blocking the Pullout of Its Stem Domain"],"prefix":"10.1002","volume":"21","author":[{"given":"Vadim S.","family":"Korotkov","sequence":"first","affiliation":[{"name":"Chemical Biology Helmholtz Centre for Infection Research  Braunschweig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peer","family":"Lukat","sequence":"additional","affiliation":[{"name":"Structure 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for Infection Research  Braunschweig Germany"},{"name":"German Center for Infection Research (DZIF)  Site Hannover\u2010Braunschweig Germany"},{"name":"Center of Biomolecular Drug Research (BMWZ) Leibniz Universit\u00e4t  Hannover 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